of Phenylketonuria (PKU)
is an inborn error of metabolism
characterized by high levels of the amino acid phenylalanine [Phe] in the blood of
newborns. PKU is
diagnosed by means of the Guthrie
devised by Dr Robert Guthrie (1916 - 1995) after the birth of
his own child with PKU.
A small drop of blood is taken from the heel of a newborn
(left) and applied to a card [right]. In the original form of
the test, a punch-out of the dried disc was incubated on a
petri dish plated with bacteria (Bacillus subtilis) in the presence of a
growth inhibitor, B-2-thienyl-alanine.
High levels of Phe in the blood sample
overcome the inhibition, and allow the bacteria to grow. If an elevated level of Phe is detected, the
child is placed on a phenylalanine-restricted
diet for the first several years (< 10 years).
This can completely offset the expected neurological effects
(below). The Guthrie test was the first widely-used perinatal
biochemical test, and since its introduction in the early
1960s has been used in >90% of North American hospitals.
The original test has been supplanted by
measurement of Phe
concentration. Children in families at risk for PKU may also be screened by
prenatal PCR-based DNA tests for the PKU-related alleles
Recent evidence suggests that high levels
of [Phe] may impair
mental performance later in life, and that a Phe-restricted
diet should be maintained throughout life.